Glucagon-Like Peptide 1 Attenuates Lipotoxicity-Induced Islet Dysfunction in ApoE–/– Mice
Authors Liu F, Gong L, Qin W, Cui C, Chen L, Zhang M
Received 14 May 2020
Accepted for publication 8 July 2020
Published 28 July 2020 Volume 2020:13 Pages 2701—2709
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Antonio Brunetti
Fuqiang Liu,1– 4 Lei Gong,1– 4 Weidong Qin,5 Chen Cui,1– 4 Li Chen,1– 4 Mingxiang Zhang5
1Department of Endocrinology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases, Shandong University, Jinan 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People’s Republic of China; 5Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan Shandong 250012, People’s Republic of China
Correspondence: Li Chen
Department of Endocrinology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China
, Tel +86-531-8216-9255
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China
, Tel +86-531-8216-9255
Aim: Glucagon-like peptide-1 (GLP1) is known to decrease glucagon release and may be beneficial for the reduction of elevated blood glucose. However, its role and mechanism of action in diabetes remain elusive. This study aimed to examine the function of GLP1 and analyze the mechanism of effect that GLP1exerts on inducible nitric oxide synthase (iNOS) in diabetic mice.
Methods: A diabetes model was established in ApoE–/– mice fed a high-fat diet and treated with GLP1 and/or lentivirus-expressing PARP1. PARP1, iNOS, and inflammatory factors in islets were detected by Western blot and ELISA. Islet α cells and β cells and CD8+ T lymphocytes were detected by immunostaining. Islet-cell apoptosis was detected by TUNEL.
Results: GLP1 inhibited the expression of PARP1 and iNOS in islets, alleviated decrease in β cells, and suppressed cell apoptosis induced by the high-fat diet. Moreover, GLP1 recovered the decline in insulin sensitivity and glucose tolerance in ApoE–/– mice fed the high-fat diet, and the effects of GLP1 were related to the inhibition of COX2 and NFκB expression.
Conclusion: GLP1 significantly alleviated the decrease in β-cell numbers, suppressed β-cell apoptosis induced by the high-fat diet, inhibited the expression of iNOS, and alleviated inflammatory islet injury via inhibiting the COX2–NFκB pathway.
Keywords: GLP1, islet function, PARP1
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